Changes in heparan sulfate structure during transition from the proliferating to the non-dividing state of cultured arterial smooth muscle cells

Cultured arterial smooth muscle cells synthesize a cell-associated heparan sulfate proteoglycan which consists of a 92 kDa core protein with 3 to 4 heparan sulfate side chains covalently attached. Biosynthesis of the cell-associated heparan sulfate proteoglycan was compared in proliferating and in non-dividing vascular smooth muscle cells which are preincubated in the presence of 35]sulfate or a combination of 35S]methionine and 3H]glucosamine. The Mr of the core protein was identical in either growth state, but changes in the structure of the heparan sulfate side chains were observed. Non-dividing (postconfluent) arterial smooth muscle cells form longer heparan sulfate chains with a higher proportion of hydrophobic (N-acetyl) groups than proliferating (preconfluent) cells as judged from gel filtration experiments, hydrophobic interaction chromatography and heparitinase degradation. An enzyme preparation from proliferating cells catalyzes deacetylation and N-sulfation of heparan sulfate at a 5-fold higher activity than from non-dividing cells. Cell density-dependent structural differences of heparan sulfate are related to the finding that heparan sulfate isolated from non-dividing cells has a 10-fold higher antiproliferative potency than heparan sulfate from proliferating (preconfluent) cells.